tbuckley/cabot-search huggingface dataset:
Regorafenib plus tislelizumab for patients with metastatic colorectal cancer: A real-world study.
Authors: Xiang Gao, Xiaoping Chen, Yutian Zhao, Yong Mao
Journal: Journal of Clinical Oncology (2023)

e15589 Background: Regorafenib improves progression-free survival (PFS) and overall survival (OS) in patients with refractory metastatic colorectal cancer (mCRC). As a multikinase inhibitor, regorafenib could regulate the immune microenvironment. We aimed to evaluate the efficacy and safety of regorafenib plus tislelizumab in patients with mCRC in a real-world setting. Methods: We retrospectively analyzed the efficacy and safety of patients with mCRC who received at least one cycle of regorafenib plus tislelizumab between Mar 10, 2021 and Dec 18, 2022 in the Affiliated Hospital of Jiangnan University. 33 patients were received regorafenib (80mg, po, qd, d1-21) every 4 weeks and tislelizumab (200mg, iv) every 3 weeks, until disease progression, intolerable toxicities, or physician/patient withdrawal. The safety and efficacy were assessed by investigators per CTCAE v5.0 and RECIST v1.1, respectively. Results: A total of 33 mCRC patients (19 male vs. 14 female, 5 second-line recipients vs. 20 third-line recipients vs. 7 fourth-line recipients vs. 1 unknown, average age of 62.6 years) were enrolled. Most patients had left-sided cancer (63.6%), liver metastases and lung metastases both occurred in 19 patients (57.6%). With a median follow-up of 6.77 months (range 0- 21.6), the objective response rate (ORR) and disease control rate (DCR) were 15.2% and 100%, with a median PFS of 12.97 months (95% CI, 9.07-NA). The median OS was 19.83 months (95%CI, 7.66-32.01). There was no significant difference in OS between patients with and without liver metastases, the mOS was 19.8 months (95%CI, 9.53-NA) vs. not reached (NR); P = 0.368. The incidence of grade 3/4 adverse events was 24.2%, the most common TRAEs of grade ≥3 were anemia (9.1%) and hyperbilirubinemia (9.1%). No new safety signals were identified. Conclusions: The combination of regorafenib and tislelizumab had a manageable safety profile and promising efficacy in mCRC patients. And this combined therapy needs further prospective studies to verify the outcomes.
Combined immune checkpoint inhibition with durvalumab and tremelimumab with and without radiofrequency ablation in patients with advanced biliary tract carcinoma.
Authors: M. Cecilia Monge B., Kelley Lauren Coffman, Donna M. Hrones, Seth M. Steinberg, Bernadette Redd, Bradford Wood, Changqing Xie, Tim F. Greten
Journal: Journal of Clinical Oncology (2023)

e16158 Background: The prognosis of advanced bile tract cancer (BTC) is unfavorable with a 5-year overall survival (OS) rate of less than 10%. Durvalumab has been approved in the first line setting in combination with chemotherapy (gemcitabine with cisplatin) for advanced BTC. Monotherapy with immune checkpoint inhibitors (ICI) in BTC in the second line is suboptimal with ORR reported in the 5-15% range. The purpose of this study was to explore the efficacy of an anti-PD-L1 (durvalumab) agent in combination with an anti-CTLA4 (tremelimumab) agent with and without radio frequency ablations (RFA) in advanced BTC. Methods: Eligible patients with advanced BTC who had received or refused at least one prior line of systemic therapy were treated with tremelimumab 75 mg intravenously (IV) and durvalumab 1500 mg (IV) for 4 combined doses followed by monthly durvalumab 1500 mg IV alone until progression of disease or unacceptable toxicity. Objective response was assessed through CT or MRI by Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) every 8 weeks. Adverse events (AEs) were recorded and managed. The primary endpoint was 6-month progression free survival (PFS). All patients underwent a pretreatment and on treatment biopsy. Results: 22 patients with advanced BTC were enrolled in this study; 10 patients were treated with durvalumab and tremelimumab (Durva/ Treme -Arm A) and 12 patients were treated with the combination of durvalumab and tremelimumab and an ablative procedure (Durva/ Treme/ RFA -Arm B). A total of 18 patients were evaluable (10 in Arm A and 8 in Arm B). The best clinical response in Arm A were as follows: PR (n=8), SD (n=1), PD (n=1) and in Arm B: SD (n=3), PD (n=5). The median progression free survival (PFS) in the Durva/ Treme Arm A was 3.3 months (95% CI: 1.9-3.9) and Durva/ Treme/ RFA Arm was 2 months (95% CI: 1.3-2.5)). The median overall survival (OS) in the Durva/ Treme Arm A was 6.1 months (95% CI: 3.5-7.4) and Durva/ Treme/ RFA Arm was 5.7 months (95% CI: 2.9-7.6). The most common study hematologic related Grade 3-4 adverse events (AEs) were lymphopenia (n=6) and anemia (n=3) and the most common non hematologic AEs included increased AST (n=9), increased alk phos (n=7) and increased total bilirubin (n=6). Conclusions: Combined ICI with Durva/ Treme with and without RFA is well tolerated; Durva/ Treme alone showed promising activity in this small early-stage study, with an ORR of 80%, in patients with advanced BTC. Clinical trial information: NCT02821754 .
Impact of cirrhosis on mortality in gastrointestinal malignancies: A retrospective study from nationwide database.
Authors: Chun-Wei Pan, Maria Cristina Cuartas Mesa
Journal: Journal of Clinical Oncology (2023)

e16324 Background: Cirrhosis is a leading cause of death in the United States, and it represents a significant cause of deterioration in the quality of life of patients worldwide. Patients with cirrhosis can be affected by malignant and non-malignant co-morbid conditions, which can impact their prognosis. Among these, gastrointestinal (GI) malignancies like colorectal, pancreatic, and hepatic represent some of the most prevalent tumors affecting the GI tract. As both cirrhosis and cancer rates rise, our study aims to explore the impact of cirrhosis on hospitalization outcomes in gastrointestinal (GI) Cancer. Methods: We used the National Inpatient sample from 2016-2020 and identified admission with a diagnosis of GI cancer using International Classification of Disease-10 codes. The cohort was further stratified into patients with a secondary diagnosis of Cirrhosis compared to those without cirrhosis. All analysis was performed using STATA V17, considering P &lt; 0.05 statistically significant. Multivariate regression analysis was used, and confounding variables adjusted were age, gender, race, insurance, and baseline hospital characteristics. Results: A total of 1,391,165 admissions with GI malignancies were identified from 2016 to 2020. Among these, 272,729 (19.6%) had a secondary diagnosis of cirrhosis, while 1,118,435 (80.4%) did not. The cirrhotic cohort was more likely to be male (71.4%) compared to the non-cirrhotic cohort (55.5%). Cirrhosis was most commonly associated with hepatocellular carcinoma (81.7%), pancreatic cancer (8.1%), and colorectal cancer (5.7%). Patients with cirrhosis have higher mortality rates in various GI cancers. This includes esophageal cancer (17.0%) compared to those without cirrhosis (10.7%), with an adjusted odds ratio of 1.55 (95% confidence interval: 1.02-2.34, P &lt; 0.05). Similarly, higher mortality rates were observed in gastric cancer (15.8%), colorectal cancer (12.6%), hepatocellular carcinoma (11.1%), biliary tract cancer (13.9%), and pancreatic cancer (11.5%) compared to those without cirrhosis, with adjusted odds ratios of 1.63, 2.06, 1.41, 1.78, and 1.41 respectively. Conclusions: In this study of 1.4 million gastrointestinal malignancy-related admissions from 2016 to 2020, 19.6% had a secondary diagnosis of cirrhosis. This cohort of patients had a higher mortality rate in various gastrointestinal cancers than those without cirrhosis. Cirrhosis was more commonly associated with hepatocellular carcinoma, followed by gastric cancer. These findings suggest that cirrhosis is a significant risk factor linked with higher mortality in gastrointestinal malignancy-related admissions. Further research is necessary to characterize this association better in order to improve outcomes for patients with cirrhosis and GI malignancies.
Metabolomic differences in young-onset versus average-onset colorectal adenocarcinoma.
Authors: Thejus Jayakrishnan, Nicole Farha, Arshiya Mariam, Daniel Miller Rotroff, Federico Aucejo, Shimoli V Barot, Madison Conces, Kanika G. Nair, Smitha S. Krishnamurthi, Stephanie Schmit, David Liska, Alok A. Khorana, Suneel Deepak Kamath
Journal: Journal of Clinical Oncology (2023)

3510 Background: Novel deleterious effects of environmental exposures may play a role in the rising incidence of young-onset colorectal cancer (yoCRC). We used metabolomics to assess differences between yoCRC and average-onset CRC (aoCRC), in comparison to healthy controls, which may provide insight into the pathogenesis and suggest any exposure risks. Methods: Patients with stage I-IV CRC and healthy controls were identified from prospective biobanks and categorized based on age &lt; 50 years (yoCRC or young controls) or age &gt; 60 years (aoCRC or older controls). Plasma metabolites were profiled using GC-TOF mass spectrometry. Differential abundance of metabolites was investigated using unadjusted and adjusted logistic regression. Metabolic pathway analysis was performed using Metaboanalyst 5.0. All p-values were adjusted for multiple testing (false-discovery rate, FDR p &lt; 0.20 considered significant). Results: The study population comprised 170 CRC patients (66 yoCRC and 104 aoCRC) and 49 healthy controls (34 young and 15 old). Association analyses revealed four differentially abundant metabolites: citrate (FDR p = 0.04), cholesterol (0.14), and two unidentified metabolites (UM). Metabolic pathways significantly altered in yoCRC vs. aoCRC included: carbohydrate metabolism (citrate cycle, FDR p = 0.04), carbohydrate biosynthesis (glyoxylate and dicarboxylate metabolism, FDR p = 0.004), amino-acid metabolism (alanine, aspartate, and glutamate metabolism, FDR p = 0.01, arginine biosynthesis, FDR p = 0.02, and amino-acid t-RNA biosynthesis, FDR p = 0.03). There were no significant metabolomic differences between young and old controls. Significant associations on survival analysis included: adipic acid with aoCRC (HR = 3.1, 95% CI = , 1.7-5.6, FDR p = 0.13, unadjusted analysis) suggesting worse survival with higher levels and 4-hydroxyhippuric acid with the whole cohort (HR = 0.4, 95% CI = 0.3-0.7, FDR p = 0.05, adjusted analyses) indicating better survival with higher levels. Conclusions: We identified significant differences in the citrate cycle - a core pathway of cellular metabolism associated with colorectal cancer. Metabolomic differences in pathways of carcinogenic significance (aspartate) and environmental exposures (arginine and dietary red meat) were also noted, suggesting potential relationships with younger age of CRC onset. [Table: see text]
Ovarian cancer and bevacizumab: Real-world use across western countries and effect on survival in high-risk subgroups.
Authors: Kristina Lindemann, Miguel Abreu, Maria de Lurdes Batarda, Dorry Boll, Anne Weng Ekmann-Gade, Jesper Hansen, Ala Jabri Haug, Claus HÃ¸gdall, Jacob Korach, Els Van Nieuwenhuysen, P. B. Ottevanger, Stephan Polterauer, Tine Henrichsen Schnack, Trude Agesen, Sofia Waldemarson, Klaus Kaae Andersen, Christian Marth
Journal: Journal of Clinical Oncology (2023)

5587 Background: Bevacizumab (bev) may be part of first-line treatment for patients with “high-risk” epithelial ovarian cancer (OC) (GOG-0218 and ICON7 trials). The prevalence of high-risk patient subgroups, including bev use and its effect on survival in a real-world setting is not well studied. Methods: The observational multi-country cohort study RESPONSE collected retrospectively medical record data on women with newly diagnosed advanced high-grade serous or endometrioid OC (DOI: 10.1002/cncr.34350). We analysed patients defined as ‘high-risk’ according to ICON7 definition as either 1) stage IV disease, 2) inoperable stage III disease or 3) sub-optimally debulked (&gt;1 cm residual disease) stage III disease. Unadjusted Cox proportional hazards regression analysis was performed to estimate the association of bev with the risk of death. Follow up time was calculated from time between response assessment at the end of primary chemotherapy and death or 20 months follow-up, whichever occurred first. Results: Of 954 patients in total, we identified 386 high-risk patients (40%) treated with platinum-based chemotherapy. Of these, 132 (34%) received bev maintenance treatment. Baseline characteristics did not differ between patients receiving bev or no bev. Bev use was associated with a statistically significant reduction in risk of death with a HR of 0.49 (95%Ci: 0.18-0.78, p=0.002) in the total group of high-risk patients. The effect on survival was most evident among inoperable stage III/IV patients (n=151) with a 63% reduction in risk of death (HR 0.37; 95% CI (0.18-0.78, p=0.009). Risk estimates for additional subgroups are given in the table. Conclusions: Forty percent of this real-world population are considered high-risk according to ICON-7 and a majority of these patients did not receive bev during first-line treatment. In line with ICON 7, this analysis supports the beneficial effect of bev on overall survival in this high-risk population. Patients who do not receive surgery are underrepresented in clinical trials and this real-world study confirms the strong benefit of bev particularly in this subgroup. Any real-world study may be limited by the potential presence of selection bias of patients to receive bevacizumab or not. [Table: see text]
The effect of formal education on ovarian cancer, clinical trial access, and clinical trial awareness among Black and Latino US women.
Authors: Ozlem Equils, Amonda Bakaj, Klaudi Lekaj, Treasure Nwokeleme, Victoria Onigbinge, Indiara Gonzalez, Cynthia Muyah, Fanesse Muyah, Brianna Rocheburn, Elsie Ureta
Journal: Journal of Clinical Oncology (2023)

e18667 Background: Ovarian Cancer (OC) is ranked as one of the deadliest women’s cancers in the US. Due to non-specific symptoms, it is often misdiagnosed and detected late. The mortality rate is higher and increasing among Black women. In addition, Black women have poor participation in clinical trials. We conducted a survey study among Black and Latino US women to understand the factors influencing their understanding of genetic risks of OC, clinical trial awareness and ability to access a clinical trial. Methods: MiOra health educators administered an electronic survey to 226 women in their communities in Houston, TX, Atlanta, GA, and Los Angeles, CA. The data was analyzed using two-sided Fisher’s Exact Test. Results: Out of the 226 respondents 63.4% were 30 years of age or younger and 22.9% had high school education or less (low education). Out of 109 respondents, 93 (85.3%) self-identified as Black or Latino. Age did not influence self-reported awareness of genetic risk for OC, clinical trials or how to locate a clinical trial (Table 1). Low education women were significantly less likely to report being knowledgeable about genetic risk factors of OC, clinical trials or locating clinical trials. Thirty out of 48, 62.5% responding low education women and 118 out of 173, 68.2% high education women reported to have an annual provider visit (p &gt; 0.05). The self-reported awareness on how to locate a trial was low in both the low (3 out of 48, 6.2%) and high education groups (34 out of 171, 19.9%, p &lt; 0.05). Only 8 out of 44 (18.1%) respondents who knew someone with OC knew how to locate clinical trials. Conclusions: These results suggest that the level of education influences Black and Latino women’s awareness of OC genetic risk factors, clinical trials and clinical trial access. However, even among college educated Black and Latino women, only a small portion reported to know how to locate a clinical trial. Both high and low education Black and Latino women reported to comply with annual provider visits. These visits may be an opportunity to close the health-literacy disparities in OC and clinical trials for Black and Latino women. [Table: see text]
Adjuvant nab-paclitaxel plus S-1 versus capecitabine plus oxaliplatin for patients with stage III gastric adenocarcinoma after D2 dissection: A multicenter, open-label, randomized phase 3 study.
Authors: Yu Pengfei, Yian Du, Zhiyuan Xu, Litao Yang, Jieer Ying, Ping Chen, Yunhai Wei, Yingjie Wu, Xiaojing Zhang, Zhilong Yan, Zhiheng Chen, Hongtao Xu, Yong Li, Zhichao Zheng, Nong Xu, Xiangdong Cheng
Journal: Journal of Clinical Oncology (2023)

4054 Background: Multiple clinical studies have shown that adjuvant chemotherapy could prolong the survival of patients after radical resection, it is necessary to explore better treatment options for patients with stage III gastric adenocarcinoma (GAC). We designed this study to evaluate the efficacy and safety of adjuvant nab-paclitaxel combined with S-1 (AS) versus capecitabine combined with oxaliplatin (CAPOX) in GAC. Methods: Patients with stage III GAC after D2 radical resection and achieved R0 resection were randomized 1:1 to receive adjuvant AS (nab-paclitaxel: 100 mg/m 2 , d1 and 8, q3w; S-1: 40-60 mg, bid, d1-14, q3w) or CAPOX (oxaliplatin: 130 mg/m 2 , d1, q3w; capecitabine: 1000 mg/m 2 , bid, d1-14, q3w) for 8 cycles. Stratification analysis was performed according to histological type (differentiated vs undifferentiated GAC) and AJCC 8 th pathological staging (ⅢA vs ⅢB and ⅢC). The primary endpoint was 3-year disease-free survival (DFS) rate, secondary endpoints were overall survival (OS) and safety. Results: Between March 20, 2020 and January 17, 2023, 313 patients were randomized to receive AS (n = 156) or CAPOX (n = 157). Baseline characteristics were generally balanced between the two groups. Median follow-up time was 5.16 months. The 1-year DFS rates were 87.14% and 70.16%, in the AS and CAPOX groups, respectively. The median DFS and 3-year DFS rates were not reached. The 1-year OS rate was 88.47% in AS group, and 63.89% in CAPOX group. At date cutoff, 12 patients (peritoneal recurrence, 1 patient; locoregional recurrence, 3 patients; distant recurrence, 8 patients) relapsed in the AS group and 16 patients (peritoneal recurrence, 4 patients; locoregional recurrence, 5 patients; distant recurrence, 8 patients; tumor marker recurrence, 1 patient) relapsed in the CAPOX group; some patients had multiple recurrence sites. 2 patients (1 patient for GAC; 1 patient for other diseases) died in the AS group and 11 patients (9 patients for GAC; 2 patients for other diseases) died in the CAPOX group. The median relative dose intensity of nab-paclitaxel was 90.32%, of S-1 was 80.77%, of oxaliplatin was 77.44% and of capecitabine was 78.55%. The incidence of adverse events (AEs) of any grade and grade 3/4 were 79.49% and 39.74% in the AS group, 72.61% and 22.93% in the CAPOX group. In the AS and CAPOX groups, neutropenia (31.63% vs 20.13%), leukopenia (29.71% vs 17.25%), anemia (27.80% vs 23.00%) and thrombocytopenia (4.15% vs 17.25%) were the most common AEs. Conclusions: Compared with CAPOX regimen, AS regimen has better survival rates and acceptable tolerability. AS provided new potential adjuvant regimen for stage III gastric cancer after D2 resection. Clinical trial information: NCT04135781 .
Palliative medicine referral trends by demographics for patients with stage IV cancer at an urban safety net hospital.
Authors: Sandhya Sharma, Catherine Reinert, Kelly Ferraro
Journal: Journal of Clinical Oncology (2023)

e18541 Background: Multiple randomized trials have shown that early referral to palliative clinic improves quality of life and has survival advantages when combined concurrently with standard oncology care in patients with advanced cancer. We reviewed data referral trend data for stage 4 cancer patients at an urban safety net hospital with the goal of characterizing demographic factors that may be associated with the amount of time both to referral and to the patient establishing care with palliative medicine in order to identify possible barriers to care. Methods: We identified patients with stage IV cancer seen in our oncology clinic from 2017-2020 using tumor registry cancer staging. We conducted a retrospective chart review of these patients. Demographic data were collected through chart review using a standardized data collection tool. We calculated data using relative frequency. Results: A total of 249 patients with Stage IV cancer were identified during this timeframe. Of these, 137 patients (55%) were referred to palliative clinic. This included 77 male and 60 female patients. The average time between the patient’s first oncology visit and a referral made to the palliative clinic was 187 days, with much higher referral time for female patients (279 days). The referral relative frequency was high among African American and Asian population of 1.46 and 1.20, respectively; with highest rate of 2.14 for African American women. Patients identifying as African and Hispanic had the lowest relative referral frequency, with 0.29 and 0.77, respectively. The average number of days between referral made and first palliative appointment was 41 days, with longer delay in female patients (54 days). The time to first appointment relative frequency was high among Asian population (4.04) and low among African (0.36) and Hispanics (0.63). Patients with Medicaid and those who were uninsured were referred to palliative clinic sooner with average of 121 days and 109 days respectively, as opposed to patients with private insurance (387 days). The appointment relative frequency was also earlier for uninsured and Medicare patients of 0.60 and 0.92, respectively. Conclusions: Our study shows that there is delay in getting palliative care referrals and appointments among African American and Asian population, and female patients. This can be due to cultural and systemic barriers: palliative care is a newer field, with a broader community understanding of its purpose and benefits still growing in many patient populations. We can improve the gap with patient-oriented targeting the identified subgroups who demonstrated more opportunity. The study also highlights more expeditious care for patients with Medicare and uninsured patients, as opposed to private insurance. These early referrals may be due to higher psychosocial needs and clinical requests for help from the palliative interdisciplinary team.